Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease

Genes
Megan Stevens, S Oltean

Abstract

Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3' splice site gives rise to a functionally different family of isoforms, termed VEGF-Axxxb, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx/VEGF-Axxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys-Drash syndrome. Using mouse models of kidney disease where the VEGF-A isoform balance is disrupted, several reports have shown that VEGF-A165b treatment/over-expression in the kidney is therapeutically beneficial. Furthermore, inhibition of certain splice factor kinases involved in the regulation of VEGF-A terminal exon splicing has provided some mechanistic insight into how VEGF-A splicing could be regulated in the kidney. This review highlights the importance of further investigation into the novel area of VEGF-A splicing in chronic kidney disease pathogenesis and how future studies may allow for the development of splicing-modifying therapeutic drugs.

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Citations

Apr 25, 2018·International Journal of Molecular Sciences·Chloe J PeachJeanette Woolard
Jun 26, 2018·International Journal of Molecular Sciences·Katsuyuki TanabeJun Wada
Apr 18, 2019·American Journal of Physiology. Renal Physiology·Katharine TookeMargaret A Vizzard
Nov 26, 2019·Chinese Medical Journal·Fei QiXin-Min Liu
Feb 29, 2020·International Journal of Molecular Sciences·Toshihiko TakeiwaSatoshi Inoue
Oct 11, 2020·Medicinal Research Reviews·Claudia RiccardiDaniela Montesarchio
Oct 16, 2021·Journal of Experimental & Clinical Cancer Research : CR·Laura MicheliLorenzo Di Cesare Mannelli

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BETA
transgenic

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